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Derek Lowe's commentary on drug discovery and the pharma industry. An editorially independent blog from the publishers of Science Translational Medicine. All content is Derek’s own, and he does not in any way speak for his employer.

Lowe's Laws of the Lab

Another Law of the Lab

This time, it’s the libelous assertion that:You should only believe yields in Tetrahedron Letters papers if you also send off for everything you see advertised on late-night TV.
Well, that’s a little unfair. Not completely unfair – just a little. There are papers in Tet Lett whose procedures are perfectly reproducible – I’ve used some of them. And on the other hand, there are impressive full papers in JACS that have steps whose efficiency could only be reproduced by angels or advanced space aliens. I shouldn’t be so hard on one particular journal. But I’ll stand by the principle behind this one, and extend it to include other brief communications in the journals that specialize in them. Chemical Communications is a worthy example from England, and Chemistry Letters gets the nod from Japan, and how.
Why the scepticism? I know that the editors of Tet Lett have been trying to remedy the situation, and things have certainly improved from the days when I wrote that law back in grad school. But people often use these journals as dumping grounds of one sort or another. When there’s not enough room to write out full experimentals, who can say you’re wrong? Three carbon-carbon bonds formed in the same reaction. . .hmmm. . .how about 85% yield? Do I hear 96%? Sold! If the scheme in the paper just has a lithium reagent drawn over an arrow, who’s to say that they didn’t optimize it out the wazoo with some esoteric blend of solvents and temperatures? Without a full experimental section, we’ll never know.
There’s always going to be a residue of doubt around a paper that lacks full details. With apologies to the non-chemists in the audience, it’s time for some lingo: You say you took off a trityl group and your THP stayed on? Show me. Tell me just how you did that, so I can see if I believe it. You say you got a 94% conversion with that exotic chiral zinc reagent? Peachy! Tell me how you made it – and that includes what kind of zinc it was, and where you bought the darn stuff. I’d like to do that reaction, too, and seeing a bunch of arrows and yields isn’t going to help me much.
The idea of the shorter-length journals (or should I say, the ideal) is that they’d be used for preliminary communications of work that would be reported in full later on. Sometimes they are, but I’d like for someone to go to the trouble of seeing just how often that really happens. No one, as far as I know, has ever done that (and I’m not holding my breath, because it’d be a bibliographic nightmare,) but it would be interesting.

3 comments on “Another Law of the Lab”

How apt your comments are.
I still remember trying to silylate an alcohol using a Tet Letts paper froma group at Merck. When we could not find any evidence of the product after running overnight recations we contacted them and found that the recommended reaction time was 14 days!
And then there are the reports from the groups of some eminent academics where many yields seemed to have been calculated as you describe!

Ahhh, yes. I always have to laugh when I see one of the heavy hitters in synthesis (one in particular, those in the biz will have a pretty good idea) reporting a 95% yield on a global deprotection on a complex substrate from hell, to give 0.5 mg of material… how good can your tare really be?

Yet another thing that drives me nuts is the reporting of extraordinary yields on reactions that aren’t likely to have been repeated. (like the aforementioned global deprotection). Don’t you have the responsibility of not reporting results that have clearly come from an n of 1? Hey, Derek, did you have a particular author in mind with that zinc comment, ’cause I sure do!!!